Article Figures & Data
Figures
- Fig. 1.
Structure of the liver. (A) Schematic showing hepatic lobular structure with cells located in a vascularized structure between the portal triad (hepatic artery, portal vein, and bile ducts) and the central vein. Hepatocytes within the lobule have varying functionality, which are roughly identified by the various zones. (B) The liver sinusoid is a dynamic environment receiving blood flow from the portal vein and hepatic artery and draining into the central vein. Nutrients and oxygen are transported through the sinusoidal endothelial cells and extracellular matrix to the hepatocytes.
- Fig. 2.
Capturing hepatic mass transport in in vitro models. (A) Device with endothelial cell–like barrier, separating flow from cell culture area, regulating nutrient flow through the intervening barrier (Lee et al., 2007). (B) Microfluidic bilayer model for culturing hepatocytes in collagen gel and flow, demonstrating in situ production of collagen for hepatic stabilization (Hegde et al., 2014). (C) Incorporation of multiple cells within the microfluidic bilayer model to mimic the liver sinusoid, and extending hepatic culture to 4 weeks (Prodanov et al., 2016). (D) Cone and plate model for hepatocyte culture, capturing aspects of interstitial flow and hemodynamics (Dash et al., 2013).
- Fig. 3.
Hepatic zonation in in vitro models. (A) Hepatic zonation in the liver sinusoid results in hepatocytes with distinct enzymatic and metabolic functionality along the length of the sinusoid. (B) Flat-plate bioreactor model to generate zonation with active oxygen consumption in the direction of media flow (Allen et al., 2005). Gas exchanger (O2, CO2, N2) upstream oxygenates the media and is consumed along the length of the bioreactor. (C) Microfluidic device with a gradient generator to create hormonal/chemical gradients across multiple hepatocytes (McCarty et al., 2016).
- Fig. 4.
Oxygen transport for optimal hepatocyte culture. (A) Microfluidic device for hepatocyte culture in a collagen gel incorporating a gas-permeable membrane (Bader et al., 1998). (B) Cross section of a microfluidic device with a gas perfusion channel sandwiched within PDMS layers for optimal hepatocyte function (Kane et al., 2006).
- Fig. 5.
Dilution effects in in vitro systems. (A) Microfluidic device with reduced media-to-cell ratio to capture primary metabolite toxicity in an hepatocyte-breast cancer model system (Bale et al., 2015b). (B) Effect of small volumes in maintaining the differentiated phenotype of hepatocytes in a microchamber culture (Haque et al., 2016).
